1. Technical Field
The present disclosure relates to the field of Optical Coherence Tomography (OCT). More particularly, the present disclosure relates to apparatus and methods for non-invasive assessment of transplant kidney viability using OCT.
2. Background of Related Art
A. The Need for a Better Test to Predict Post-Transplant Renal Outcome
More than half a million US residents have end-stage renal disease (ESRD), which is associated with high mortality rates (157.3 deaths per 1,000 patient years) and a huge economic burden (more than $30 billion per year) [1]. The treatment options for ESRD include dialysis and kidney transplantation. Transplantation is the preferred option because it promises to extend the patients' lives and also improve their life quality. Currently, with over 77,500 patients annually waiting for kidney transplants, organ shortages pose a major problem in kidney transplantation. While the vast majority of kidneys used for transplantation are obtained from heart-beating cadavers, many kidneys available for transplant are not utilized because of their unknown status (i.e., from non-heart beating cadavers, long storage times, etc.).
Also, ischemic insult suffered by cadaver kidneys awaiting transplantation frequently causes acute tubular necrosis (ATN) leading to varying degrees of delayed graft function (DGF) after transplantation, which represents a significant risk for eventual graft and patient survival[2], and can be difficult to discern from rejection. The incidence of DGF is estimated to be 15-70% [3]. Unfortunately, in present clinical practice, there is no reliable test to determine the viability of donor kidneys and whether or not donor kidneys might exhibit DGF. A timely biochemical analysis of kidneys has proven disappointing with no biochemical criteria proving accurate[4]. Therefore, there is a critical need for objective and reliable tests to predict post-transplant outcome to use organs safely and utilize the donor pool optimally.
B. Non Invasive Imaging to Predict Post-Transplant Renal Outcome
Conventional light microscopy of excision kidney biopsies are not as useful to evaluate kidney pathology as non-invasive imaging procedures because of dramatic destructive artifacts to the kidney tubules associated with such biopsies [5]. In addition, unlike non-invasive imaging procedures, excision biopsies are destructive to kidneys, take time to analyze, and image only small segments of the kidney (i.e., cannot provide global imaging of numerous regions across the kidney surface). Previous studies by one of us (Andrews et al.) have shown that a non-invasive imaging technique termed tandem scanning confocal microscopy (TSCM) could be used to determine the degree of ATN by analyzing the superficial nephrons of living rabbit donor kidneys [6]. Using TSCM, Andrews et al. observed that the histopathological changes (e.g., ATN) of superficial proximal tubules of rabbit kidneys for transplant correlated closely with subsequent post-transplant renal function[7] (see FIGS. 1A-1F taken from Andrews et al., Nephron, 2002 [7]).
FIGS. 1A-1D show TSCM images of subcapsular proximal convoluted tubules of a rabbit kidney 1 hour (FIG. 1A), 24 hours (FIG. 1B), 48 hours (FIG. 1C) and 72 hours (FIG. 1D) following harvesting. With increasing storage time, TSCM images depict the degeneration of the superficial proximal tubules. FIG. 1E illustrates a summary of the serum creatinine (SCr) in mg/dL versus various days following transplantation and FIG. 1F illustrates a summary of blood urea nitrogen (BUN) values in mg/dL measured at various days post-transplantation. As the storage time increased the post-transplant SCr and BUN values increased. All the rabbits in the 24-, 48-, and 67-hour groups exhibited various degrees of DGF but eventually survived. SCr and BUN returned to normal values. All rabbits in the 72-hour group eventually died of uremia. This is not surprising in that the status of superficial proximal convoluted tubules is indicative of the status of proximal convoluted tubules throughout the entire kidney cortex.
Other investigators have also used near-infrared confocal microscopy [8] and multi-photon microscopy [9-11] to demonstrate the ability to perform non-invasive imaging of kidney structure and function in animal models. However, the maximum penetration depth associated with these microscopy procedures is limited (about 100 μm for TSCM), which makes it difficult to impossible to non-destructively image the human kidney using the foregoing non-invasive imaging microscopic techniques, especially if it is surrounded by an intact human renal capsule. Indeed, in a previous clinical trial, the inventors of the present application found that the limited penetrating ability of TSCM precluded them from imaging human donor kidneys even when an attempt was made to remove the renal capsule [unpublished observations]. Also, conventional bulky systems TSCM are awkward in orientating the kidney specimens and especially difficult when attempting to image the kidney in situ.